Pharmacology Seminar Series: Francis McCormack, MD "role of osteoclasts in pulmonary disease"

"Role of osteoclasts in pulmonary disease"

While studying a murine model of the rare lung disease pulmonary alveolar microlithiasis, produced by deleting the    sodium phosphate co-transporter Npt2b from the pulmonary epithelium, we found that the lung responds to this particulate challenge by recruiting and reprogramming luminal monocytes to become osteoclasts in an attempt to dissolve the hydroxyapatite microliths. The animals also developed alveolar proteinosis,  which suggested similarities with another particulate-induced lung disease, silicoproteinosis/accelerated silicosis. We postulated that particulate challenge induces a stereotypical reprioritization of myeloid differentiation away from surfactant metabolizing alveolar macrophages, and toward acid and protease producing osteoclasts, resulting in accumulation of surfactant and development of pulmonary fibrosis. 

Francis McCormack, MD, Professor and Director, Division of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati

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